Bromide-mediated ortho-deprotonation in the synthesis of chiral, nonracemic ferrocene derivatives

Article abstract of DOI:10.1021/om7003282

Bromide-mediated methods for the synthesis of 1,2,3- and 1,3-substituted ferrocenes are described. Starting from monosubstituted ferrocene derivatives {Fc-R¹, R¹ = 1-dimethylaminoethyl [CH(NMe ₂)Me],p-tolylsulfinyl [4-MeC₆H₄S(O)], (2-methoxymethylpyrrolidin-1-yl)methyl [2-MeOCH₂(C₄H ₇N)CH₂], ephedrine derivative CH2N(Me)CH(Me)CH(Ph)OMe, and dimethylaminomethyl [CH₂(NMe₂)]) achiral, racemic and chiral, nonracemic 1,2,3-trisubstituted ferrocene derivatives are accessible through two consecutive ortho-lithiations. In the first deprotonation step bromide is introduced stereoselectively into position 2. In the second step, the use of Li-TMP (TMP = 2,2,6,6-tetramethylpiperidine) as the base leads to deprotonation of the ori/20-position next to bromide, and subsequent reaction with different electrophiles gives a variety of 1,2,3-trisubstituted ferrocene derivatives. Removal of the central bromide substituent leads to 1,3-disubstituted derivatives, including pincer-type ferrocene ligands.

Full text of DOI:10.1021/om7003282

3850
Organometallics 2007, 26, 3850-3859
Bromide-Mediated ortho-Deprotonation in the Synthesis of Chiral,
Nonracemic Ferrocene Derivatives
Marianne Steurer,† Yaping Wang,† Kurt Mereiter,‡ and Walter Weissensteiner*,†
Faculty of Chemistry, UniVersity of Vienna, Wa¨hringer Strasse 38, A-1090 Vienna, Austria, and Faculty of
Chemistry, Vienna UniVersity of Technology, Getreidemarkt 9/162SC, A-1060 Vienna, Austria
ReceiVed April 4, 2007
Bromide-mediated methods for the synthesis of 1,2,3- and 1,3-substituted ferrocenes are described.
Starting from monosubstituted ferrocene derivatives {Fc-R1, R1 ) 1-dimethylaminoethyl [CH(NMe2)-
Me], p-tolylsulfinyl [4-MeC6H4S(O)], (2-methoxymethylpyrrolidin-1-yl)methyl [2-MeOCH2(C4H7N)CH2],
ephedrine derivative CH2N(Me)CH(Me)CH(Ph)OMe, and dimethylaminomethyl [CH2(NMe2)]} achiral,
racemic and chiral, nonracemic 1,2,3-trisubstituted ferrocene derivatives are accessible through two
consecutive ortho-lithiations. In the first deprotonation step bromide is introduced stereoselectively into
position 2. In the second step, the use of Li-TMP (TMP ) 2,2,6,6-tetramethylpiperidine) as the base
leads to deprotonation of the ortho-position next to bromide, and subsequent reaction with different
electrophiles gives a variety of 1,2,3-trisubstituted ferrocene derivatives. Removal of the central bromide
substituent leads to 1,3-disubstituted derivatives, including pincer-type ferrocene ligands.
with these substitution patterns have been prepared using routes
involving either one or two enantio- or diastereoselective
lithiations of appropriate mono- or 1,1′-disubstituted precur-
sors.6,7 For example, most enantiopure 1,2-di- and 1,2,3-
trisubstituted ferrocenes have been prepared starting from a
monosubstituted derivative Fc-Rc, where Rc is a stereogenic
directing group (Scheme 1, route 1). After a diastereoselective
ortho-lithiation and reaction with an electrophile, 1,2-disubsti-
tuted derivatives are obtained. A number of such directing
groups can also promote a second ortho-lithiation, and this
provides access to 1,2,3-trisubstituted derivatives. In many cases,
a further step can be carried out in which the stereogenic
directing group Rc is replaced by a third substituent R3.
Interestingly, applications of chiral, nonracemic 1,3-disub-
stituted ferrocenes are very rare, a situation that might be due
to the fact that until very recently suitable methods for the
synthesis of both achiral and chiral 1,3-disubstituted derivatives
were severely lacking.2c,3,5d However, in 2002 Koridze8sas well
as Brown, van Koten, and co-workers9sextended the concept
of aryl-based pincer ligands to the ferrocene backbone10 and a
search for short and facile routes to chiral, nonracemic 1,3-
disubstituted ferrocenes was initiated. Originally, highly enan-
tiomerically enriched 1,3-disubstituted ferrocenes were obtained
Introduction
At present, enantiopure ferrocene derivatives are mainly used
as ligands for homogeneous enantioselective catalysts,1 but these
compounds have also found applications in a number of other
fields including polymer chemistry,2 liquid crystal chemistry,3
electrochemistry,4 and bioorganometallic chemistry.5 Most of
the ferrocene-based catalyst ligands in use are 1,2-disubstituted
derivatives. In addition, several higher substituted ferrocenes
such as 1,1′,2-tri-, 1,2,3-tri-, or 1,1′,2,2′-tetrasubstituted deriva-
tives have been found to give excellent performance as catalyst
ligands in asymmetrically catalyzed reactions. Almost all ligands
* Corresponding author. E-mail: walter.weissensteiner@univie.ac.at.
† University of Vienna.
‡ Vienna University of Technology.
(1) (a) Gomez Arraya´s, R.; Adrio, J.; Carretero, J. C. Angew. Chem.,
Int. Ed. 2006, 45, 7674-7715. (b) Barbaro, P.; Bianchini, C.; Giambastiani,
G.; Parisel, S. L. Coord. Chem. ReV. 2004, 248, 2131-2150. (c) Colacot,
T. J. Chem. ReV. 2003, 103, 3101-3118. (d) Dai, L.-X.; Tu, T.; You, S.-
L.; Deng, W.-P.; Hou, X.-L. Acc. Chem. Res. 2003, 36, 659-667. (e)
Catalytic Asymmetric Synthesis; Ojima, I., Ed., Wiley-VCH: New York,
2000.
(2) (a) Abd-El-Aziz, A. S.; Shipman, P. O. In Frontiers in Transition
Metal-Containing Polymers; Abd-El-Aziz, A. S., Manners, I., Eds.; Wiley:
New York, 2007; pp 45-133. (b) Hida, N.; Takei, F.; Onitsuka, K.; Shiga,
K.; Asaoka, S.; Iyoda, T.; Takahashi, S. Angew. Chem., Int. Ed. 2003, 42,
4349-4352. (c) Plenio, H.; Hermann, J.; Sehring, A. Chem.-Eur. J. 2000, 6,
1820-1829. Dendrimers: (d) Mery, D.; Astruc, D. Coord. Chem. ReV. 2006,
250, 1965-1979. (e) Routaboul, L.; Vincendeau, S.; Turrin, C.-O.;
Caminade, A.-M.; Majoral, J.-P.; Daran, J.-C.; Manoury, E. J. Organomet.
Chem. 2007, 692, 1064-1073. (f) Kollner, C.; Togni, A. Can. J. Chem.
2001, 79, 1762-1774.
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P.; Lloveras, V.; Vidal-Gancedo, J.; Rovira, C.; Veciana, J.; Evans, D. J.;
Wurst, K. Chem.-Eur. J. 2004, 10, 1815-1826. (b) Sutcliffe, O. B.; Bryce,
M. R.; Batsanov, A. S. J. Organomet. Chem. 2002, 656, 211-216. (c)
Takeuchi, M.; Mizuno, T.; Shinkai, S.; Shirakami, S.; Itoh, T. Tetrahe-
dron: Asymmetry 2000, 11, 3311-3322.
(5) (a) van Staveren, D. R.; Metzler-Nolte, N. Chem. ReV. 2004, 104,
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Schatte, G.; Kraatz, H.-B. Angew. Chem., Int. Ed. Engl. 2006, 45, 6882-
6884. (d) Ferber, B.; Top, S.; Vessieres, A.; Welter, R.; Jaouen, G.
Organometallics 2006, 25, 5730-5739.
(6) (a) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J. Chem. Soc. ReV.
2004, 33, 313-328. (b) Ferrocenes: Homogeneous Catalysis, Organic
Synthesis, Materials Science; Togni, A., Hayashi, T., Eds.; VCH: Weinheim,
1995.
(7) Clayden, J. In Chemistry of Organolithium Compounds; Rappoport,
Z., Marek, I., Eds.; Wiley: Chichester, 2004; pp 495-646.
(8) Koridze, A. A.; Sheloumov, A. M.; Kuklin, S. A.; Lagunova, V. Y.;
Petukhova, I. I.; Dolgushin, F. M.; Ezernitskaya, M. G.; Petrovskii, P. V.;
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(9) Farrington, E. J.; Martinez Viviente, E.; Williams, B. S.; van Koten,
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(10) For achiral ferrocene-based pincer ligands see also: (a) Kuklin, S.
A.; Sheloumov, A. M.; Dolgushin, F. M.; Ezernitskaya, M. G.; Peregudov,
A. S.; Petrovskii, P. V.; Koridze, A. A. Organometallics 2006, 5, 5466-
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D.; Lagunova, V. Y.; Petukhova, I. I.; Ezernitskaya, M. G.; Peregudov, A.
S.; Petrovskii, P. V.; Vorontsov, E. V.; Baya, M.; Poli, R. Organometallics
2004, 23, 4585-4593.
10.1021/om7003282 CCC: $37.00 © 2007 American Chemical Society
Publication on Web 06/19/2007

Bromide-Mediated ortho-Deprotonation
Organometallics, Vol. 26, No. 15, 2007 3851
Scheme 1. General Reaction Schemes for the Synthesis of
1,2-Di-, 1,2,3-Tri-, and 1,3-Disubstituted Ferrocenes
Scheme 2. Sulfoxide-Mediated Synthesis of
1,3-Disubstituted Ferrocenes (from ref 19)
from racemates11 by separating the enantiomers using different
resolution methods.12 However, the lack of both general methods
for the synthesis of the racemates and efficient resolution
methods meant that pure enantiomers were obtained only on a
rather small scale.
In 2004, Brown and co-workers reported a broadly applicable
method for the synthesis of achiral or racemic 1,3-disubstituted
ferrocene derivatives, with the key step in this reaction sequence
being a selective meta-lithiation of ferrocenyl-tolyl sulfide.13
The use of this methodology enabled the synthesis of a variety
of 1,3-disubstituted ferrocenes on a larger scale. However,
attempts to run this and other reactions enantioselectively proved
unsuccessful and, in addition, methods for separating the
enantiomers of racemic mixtures are still available only to a
very limited extent. As a result, we and others became interested
in the development of general and preparatively useful methods
for the diastereoselective synthesis of chiral, nonracemic 1,3-
disubstituted ferrocenes.
As suggested several years ago by Kagan, the preparation of
1,2,3-trisubstituted precursors according to reaction route 1
(Scheme 1) and subsequent removal of the central substituent
should lead to chiral, nonracemic 1,3-disubstituted ferrocenes.14
However, this sequence requires a central substituent that can
direct sequentially and diastereoselectively to both ortho-
positions and can finally be replaced by a proton. Sulfinyl and,
to a lesser extent, sulfonyl groups might be considered for this
purpose. For a racemic derivative this sequence had already been
carried out in 1974 by Slocum and co-workers, who used
chloride as the central ortho-directing group Rc.15
intermediates are obtained in two steps, both of which involve
ortho-deprotonation reactions. Subsequent removal of the central
substituent (Rc) gives 1,3-disubstituted ferrocenes. In this case
the central substituent Rc must be both ortho-directing and
removable, although stereogenicity is not required. This allows
for a broader range of possible candidates for Rc, including the
halides (chloride and bromide) as well as sulfinyl and sulfonyl
groups.
In preliminary studies we evaluated this reaction sequence
by using chloride, bromide,16 and the p-tolylsulfinyl group17 as
the central substituent Rc. In our opinion bromide was best suited
for this purpose, since the removal of chloride from the ferrocene
backbone (in comparison to bromide) requires much more
vigorous reaction conditions, while the stereogenic p-tolylsulfi-
nyl group must be introduced with the appropriate relative
configuration to allow for the second ortho-deprotonation step.
This can be achieved, for example, by diastereoselective
oxidation of sulfides12a,18 or, as reported very recently by Jaouen,
Top, and co-workers, by transferring the p-tolylsulfinyl group
with use of a chiral reagent (Scheme 2, step A f B).19 The use
of the latter approach gave 1,3-disubstituted ferrocene deriva-
tives in good yields, but this methodology requires two
stereogenic ortho-directing groups.
Our approach to chiral, nonracemic 1,3-disubstituted fer-
rocenes also follows reaction route 2 (Scheme 1) but with
bromide as the central substituent. In a recent communication
we reported that (i) bromide can be used in combination with
a number of stereogenic ortho-directing groups R1, (ii) ortho-
deprotonation next to bromide can be achieved in high yield,
and (iii) bromide can be easily exchanged by other electro-
philes.20 In addition, we realized that in several cases in the
second ortho-lithiation step the original ortho-directing group
R1 competed with bromide, and deprotonation next to bromide
as well as next to R1 was observed. In such cases R1 had to be
transformed into a nondirecting substituent R′ (Scheme 3). We
now describe in detail bromide-mediated synthesis routes to
Alternatively, a second reaction sequence (Scheme 1, route
2) seems to be suitable to build up chiral, nonracemic ferrocene
derivatives diastereoselectively: starting from an appropriate
monosubstituted ferrocene derivative (Fc-R1), 1,2,3-trisubstituted
(11) (a) Bonini, B. F.; Capito`, E.; Comes-Franchini, M.; Fochi, M.; Ricci,
A. ARKIVOC 2006, 85-96. (b) Lindsell, W. E.; Xinxin, L. J. Chem. Res.
1998, (S) 62-63; (M) 423-433. (c) Bickert, P.; Hildebrandt, B.; Hafner,
K. Organometallics 1984, 3, 653-657. (d) Leigh, T. J. Chem. Soc. 1964,
3294-3302. (e) Rosenblum, M.; Woodward, R. B. J. Am. Chem. Soc. 1958,
80, 5443-5449.
(12) (a) D’Antona, N.; Lambusta, D.; Morrone, R.; Nicolosi G.; Secundo,
F. Tetrahedron: Asymmetry 2004, 15, 3835-3840. (b) Chuard, T.; Cowling,
S. J.; Fernandez-Ciurleo, M.; Jauslin, I.; Goodby, J. W.; Deschenaux, R.
Chem. Commun. 2000, 21, 2109-2110. (c) Izumi, T.; Hino, T. J. Chem.
Technol. Biotechnol. 1992, 55, 325-331. (d) Yamazaki, Y.; Uebayasi, M.;
Hosono, K. Eur. J. Biochem. 1989, 184, 671-80. (e) Haller, G.; Schlo¨gl,
K. Monatsh. Chem. 1967, 98, 603-618.
(13) Pichon, C.; Odell B.; Brown, J. M. Chem. Commun. 2004, 598-
599.
(14) Rebiere, F.; Riant, O.; Ricard, L.; Kagan, H. B. Angew. Chem., Int.
Ed. Engl. 1993, 32, 568-570.
(15) Slocum, D. W.; Marchal R. L.; Jones, W. E. Chem. Commun. 1974,
967-968.
(16) Steurer, M. Diploma Thesis, University of Vienna, 2005.
(17) Tiedl, K. Diploma Thesis, University of Vienna, 2005.
(18) (a) Lagneau, N. M.; Chen, Y.; Robben, P. M.; Sin, H.-S.; Takasu,
K.; Chen, J.-S.; Robinson, P. D.; Hua, D. H. Tetrahedron 1998, 54, 7301-
7334. (b) Glahsl, G.; Herrmann, R. J. Chem. Soc., Perkin Trans. 1 1988,
1753-1757. (c) Herrmann, R.; Hu¨bener, G.; Ugi, I. Tetrahedron 1985, 41,
941-947.
(19) Ferber, B.; Top, S.; Welter, R.; Jaouen, G. Chem.-Eur. J. 2006,
12, 2081-2086.
(20) Steurer, M.; Tiedl, K.; Wang, Y.; Weissensteiner, W. Chem.
Commun. 2005, 4929-4931.

3852 Organometallics, Vol. 26, No. 15, 2007
Steurer et al.
Scheme 3. Bromide-Mediated Synthesis of 1,2,3-Tri- and
1,3-Disubstituted Ferrocenes
Figure 1. Molecular structure of (R,Sp)-8. Selected bond lengths
(Å): Fe-C(1-5)av ) 2.044(1), Fe-C(6-10)av ) 2.046(1), C(1)-
C(11) ) 1.509(1), C(3)-C(15) ) 1.500(2), N-C(11) ) 1.493(1),
N-C(13) ) 1.458(2), N-C(14) ) 1.463(1), C(15)-O )
1.422(1).
1,2,3-tri- and 1,3-disubstituted ferrocenes that make use of
different ortho-directing groups R1 and report how some of these
groups can be transformed easily into nondirecting functional
groups in order to prevent interference in the second ortho-
deprotonation step. Furthermore, the use of a number of different
electrophiles to introduce substituents R2 is described along with
two methods for the removal of bromide. Finally, synthetic
procedures for a few potential pincer ligands are given.
applied to the reaction of (R,Sp)-2 with Li-TMP (TMP ) 2,2,6,6-
tetramethylpiperidine) as the base and ClSiMe3 as the electro-
phile. The use of these optimized conditions gave (R,Rp)-3
exclusively (83%).
The trisubstituted derivatives (R,Rp)-4 (82%) and (R,Sp)-6
(81%) were obtained on using the electrophiles dimethylform-
amide (DMF) and ClSnBu3. Reduction of aldehyde 4 with
LiAlH4 gave alcohol (R,Rp)-5 in 92% yield. Further reaction of
3 and 5 with n-BuLi (3, 1.5 equiv; 5, 2.5 equiv) and H2O
removed the bromide substituent and resulted in the 1,3-
trisubstituted ferrocenes (R,Sp)-7 (84%) and (R,Sp)-8 (88%).
Single crystals of 8 suitable for an X-ray diffraction study could
be obtained. The molecular structure of 8 depicted in Figure 1
confirms not only the 1,3-substitution pattern but also its (R,Sp)
absolute configuration.
Results
The aromatic halides fluoride, chloride, and bromide are well
known to direct metalationsmostly lithiationsto the ortho-
positions of their aromatic backbone.21 In the case of chloro-
ferrocene this was investigated by Huffman et al. as early as
196522 and later on by Slocum and co-workers.23 As with
bromobenzenes, bromo-substituted ferrocenes can be ortho-
deprotonated using lithium diisopropylamide (LDA), and this
was described in several papers by Butler and co-workers.24
On the basis of these and our preliminary results we tested
bromide as the central substituent Rc in combination with four
stereogenic substituents (R1), 1-dimethylaminoethyl [CH(NMe2)-
Me], the p-tolylsulfinyl [4-MeC6H4S(O)] unit, (2-methoxy-
methylpyrrolidin-1-yl)methyl [2-MeOCH2(C4H7N)CH2], and the
ephedrine derivative CH2N(Me)CH(Me)CH(Ph)OMe, as well
as the nonstereogenic dimethylaminomethyl [CH2(NMe2)] group
(Scheme 3).
Sequence 1, R1 ) CH(NMe2)Me. In the first reaction
sequence [R1 ) CH(NMe2)Me (Scheme 4)] commercially
available (R)-N,N-(1-dimethylaminoethyl)ferrocene [Ugi’s amine,
(R)-1] was reacted according to a published procedure with
s-BuLi and BrCF2CF2Br to give (R,Sp)-2 in 88% yield.25 In order
to optimize the subsequent deprotonation step with respect to
temperature and the amount of base, different conditions were
It is interesting to note thatslike a p-tolylsulfinyl group
(Scheme 2, step C f D)sthe bromide substituent of 6 located
adjacent to a tributylstannyl substituent can be removed
selectively. Reaction of 6 with 1.5 equiv of tert-BuLi and H2O
gave (R,Sp)-9 (97%) exclusively. Further transformation of the
tributylstannyl group was achieved by treating 9 with 1.2 equiv
of n-BuLi. Subsequent reaction with electrophile DMF or I2
resulted in aldehyde (R,Sp)-10 (87%) and iodo derivative (R,Sp)-
11 (72%). It should be mentioned that attempts to replace the
tributylstannyl group of 9 by iodide under standard conditions
(I2/CH2Cl2, Scheme 2, step D f E) resulted in product mixtures,
since under these reaction conditions the dimethylamino group
is partially oxidized to an acetyl group. As an example for a
further functional group transformation, we synthesized ami-
nophosphine (R,Sp)-12 (67%).26 In summary, reaction sequence
1 provides a facile, high-yielding route to a number of differently
substituted chiral, nonracemic 1,3-disubstituted ferrocenes. For
example, amino alcohol (R,Sp)-8 was obtained in four steps from
(R)-1 in 58% overall yield.
(21) (a) Clayden, J. Organolithiums: SelectiVity for Synthesis; Perga-
mon: Amsterdam, 2002; pp 58-59. (b) Mongin, F.; Schlosser, M.
Tetrahedron Lett. 1996, 37, 6551-6554.
(22) Huffman, J. W.; Keith, L. H.; Asbury, R. L. J. Org. Chem. 1965,
30, 1600-1604.
(23) (a) Slocum, D. W.; Jennings, C. A.; Engelmann, T. R.; Rockett, B.
W.; Hauser, C. R. J. Org. Chem. 1971, 36, 377-381. (b) Slocum, D. W.;
Koonsvitsky, B. P.; Ernst, C. R. J. Organomet. Chem. 1972, 38, 125-132.
(24) (a) Butler, I. R.; Drew, M. G. B. Inorg. Chem. Commun. 1999, 2,
234-237. (b) Butler, I. R.; Mu¨ssig, S; Plath, M. Inorg. Chem. Commun.
1999, 2, 424-427. (c) Butler, I. R.; Drew, M. G. B.; Greenwell, C. H.;
Lewis, E.; Plath, M.; Mu¨ssig, S.; Szewczyk, J. Inorg. Chem. Commun. 1999,
2, 576-580.
(25) (a) Han, J. W.; Tokunaga, N.; Hayashi, T. HelV. Chim. Acta 2002,
85, 3848-3854. For alternative methods see: (b) Taylor, C. J.; Roca, F.
X.; Richards, C. J. Synlett 2005, 2159-2162. (c) Barbaro, P.; Bianchini,
C.; Giambastiani, G.; Togni, A. Tetrahedron Lett. 2003, 44, 8279-8283.
(d) Pugin, B.; Landert, H.; Pioda, G. (Novartis A.-G., Switz.) PCT Int. Appl.
WO 9815565, 1998.
Sequence 2, R1 ) 4-MeC6H4S(O). In the second reaction
sequence, the use of bromide as the central substituent was
combined with the ortho-directing p-tolylsulfinyl substituent [R1
) 4-MeC6H4S(O) (Scheme 5)]. It was anticipated that this
sequence could complement the methodology recently reported
by Brown and co-workers for the synthesis of racemic deriva-
tives.13 Bromide (R,Sp)-14 was prepared according to literature
(26) For the synthesis methodology see: Cabou, J.; Brocard, J.; Pe´linski,
L. Tetrahedron Lett. 2005, 46, 1185-1188.

Bromide-Mediated ortho-Deprotonation
Organometallics, Vol. 26, No. 15, 2007 3853
Scheme 4. Synthesis of 1,3-Disubstituted Ferrocenes, Sequence 1
Scheme 5. Synthesis of 1,3-Disubstituted Ferrocenes,
Sequence 2
Scheme 6. Synthesis of 1,3-Disubstituted Ferrocenes,
Sequence 3
procedures by reacting p-tolyl-ferrocenyl sulfoxide (R)-1327 with
LDA and BrCF2CF2Br (85%),24a and the product was subse-
quently reduced with sodium iodide and chlorotrimethylsilane28
to give sulfide (Sp)-15 (84%). On using Li-TMP ortho-
deprotonation occurred selectively adjacent to the bromide
substituent, and subsequent reaction with DMF gave aldehyde
(Sp)-16 in 74% yield. Reduction with LiAlH4 resulted in alcohol
(Sp)-17 (83%), which on reaction with n-BuLi and H2O led to
the desired 1,3-disubstituted ferrocene derivative (Rp)-18 (92%).
Overall, 18 is accessible from 13 in 40% yield, and as recently
reported for its racemate,13 18 can easily be functionalized and
can therefore serve as a valuable starting material for a variety
of chiral, nonracemic 1,3-disubstituted ferrocene derivatives.
Sequence 3, R1) 2-MeOCH2(C4H7N)CH2. The third reac-
tion sequence involves the use of bromide as the central
substituent together with the (2-methoxymethylpyrrolidin-1-yl)-
methyl substituent [2-MeOCH2(C4H7N)CH2] as the ortho-
directing group R1 (Scheme 6). Bromide (R,Rp)-20 was prepared
by reacting (R)-1929 with s-BuLi and either BrCF2CF2Br (81%)
or Br2CHCHBr2 (74%).30 However, when 20 was treated with
Li-TMP followed by DMF as the electrophile, a mixture of
aldehydes was obtained in which (R,Sp)-21 was the main
component. Reduction of this mixture with NaBH4 led to the
isolation of alcohol (R,Sp)-22 in 83% yield.
In contrast to bromide 2, in this case deprotonation occurred
predominantly next to the stereogenic ortho-directing group
rather than next to the bromide substituent. In order to
circumvent this problem, we reasoned that protection of the
nitrogen lone pair could reverse the direction of ortho-
deprotonation. Hence, (R,Rp)-20 was reacted with BH3(THF)
(27) (a) Guillaneux, D.; Kagan, H. B. J. Org. Chem. 1995, 60, 2502-
2505. (b) Riant, O.; Argouarch, G.; Guillaneux, D.; Samuel, O.; Kagan, H.
B. J. Org. Chem. 1998, 63, 3511-3514. (c) Rebiere, F.; Samuel, O.; Kagan,
H. B. Tetrahedron Lett. 1990, 31, 3121-3124. (d) Cotton, H. K.; Huerta,
Fernando F.; Ba¨ckvall, J.-E. Eur. J. Org. Chem. 2003, 2756-2763.
(28) For the synthesis methodology see: Olah, G. A.; Narang, S. C.;
Gupta, B. G. B.; Malhotra, R. Synthesis 1979, 61-62.
(30) Pugin, B.; Feng, X. (Solvias A.-G., Switz.) PCT Int. Appl. WO
2006114438, 2006.
(29) Ganter, C.; Wagner, T. Chem. Ber. 1995, 128, 1157-1161.

3854 Organometallics, Vol. 26, No. 15, 2007
Steurer et al.
Scheme 7. Synthesis of 1,3-Disubstituted Ferrocenes,
Sequence 4
Scheme 8
Reaction of 27 with t-BuLi and BrCF2CF2Br gave (1R,2S,Rp)-
28 in 87% yield.32a All attempts to selectively ortho-deprotonate
bromide 28 led to product mixtures. In addition, unlike in the
case of 20, reaction of 28 with BH3(THF) resulted in diastereo-
meric boron complexes that showed a high tendency for
deprotection in THF. To overcome this problem, we decided
to transform the ortho-directing O-methylephedrine unit into
nondirecting functional groups, and we suspected that a silyl-
protected hydroxyl or a boron-protected dimethylamino group
would be appropriate.
As depicted in Scheme 8, bromide (1R,2S,Rp)-28 was reacted
with acetic anhydride to give acetate (Rp)-29 (79%),33 and after
saponification to alcohol (Rp)-30 (96%),34 the hydroxyl group
was protected as a tert-butyldimethylsilyl ether [(Rp)-31, 99%].
On the other hand, reaction of 28 with CH3I followed by
Me2NH gave amine (Rp)-39 (81%),32a,35 which on reaction with
BH3(THF) resulted in the very stable boron complex (Rp)-40
(98%). It is important to note that (Rp)-29 and (Rp)-39 are also
accessible from (R,Rp)-20 in 81% and 70% yield, respectively
(Scheme 8).
After transforming the O-methylephedrine unit of 28 into the
tert-butyldimethylsilyl-protected hydroxyl group (31, 75%
overall yield, based on 28), the reaction conditions optimized
for 2 (Li-TMP, DMF) were used for the selective transformation
of bromide (Rp)-31 (Scheme 7) into aldehyde (Sp)-32 (79%),
which, after reduction with LiAlH4, gave alcohol (Rp)-33 (82%).
Finally, reaction with n-BuLi and H2O removed the bromide
and gave the 1,3-disubstituted ferrocene derivative (Sp)-36 in
90% yield (44% overall, based on 28). When the ortho-
substitution reaction of (Rp)-31 was carried out with electrophile
ClSiMe3 or (4-MeC6H4S)2 the 1,2,3-trisubstituted derivatives
(Sp)-34 (58%) and (Sp)-35 (83%) were obtained. Interestingly,
reaction of 34 and 35 with n-BuLi and H2O not only removed
the bromide substituent but also induced a retro-Brook rear-
rangement,36 which led to the undesired derivatives (Sp)-37 and
(Rp)-38 in 85% and 77% yield, respectively. In order to avoid
this problem, (Sp)-35 was deprotected with tetrabutylammonium
fluoride, and this provided another route to (Sp)-17, which as
described above (Scheme 5) can be debrominated to the 1,3-
disubstituted derivative (Rp)-18.
and boron complex 23 was obtained in 95% yield. It should be
mentioned that, in principle, complexation of 20 might be
expected to give two diastereomers with opposite absolute
configuration at the nitrogen. However, only one diastereomer
was observed. Chromatography of the product led to partial
deprotection, and it was therefore used for the next reaction
without further purification. As in the case of 2, complex 23
could be deprotonated with Li-TMP next to bromide, and
reaction with DMF as the electrophile gave the desired aldehyde.
However, this intermediate aldehyde proved to be rather unstable
and was therefore reacted immediately after workup. Reduction
with NaBH4 and deprotection with diethylamine resulted in
(R,Sp)-24 in 84% yield (based on 23). Removal of bromide with
n-BuLi and H2O led to enantiopure 1,3-disubstituted ferrocene
(R,Rp)-25 (88%). Based on 19 the 1,3-disubstituted derivative
25 was prepared in 52-57% overall yield and, as an example
of an application, was subsequently transformed into pincer
ligand (R,Rp)-26 (74%).31
Sequence 4, R1 ) CH2N(Me)CH(Me)CH(Ph)OMe. The
fourth reaction sequence starts from the O-methylephedrine-
substituted ferrocene derivative (1R,2S)-27 [R1 ) CH2N(Me)-
CH(Me)CH(Ph)OMe, (Scheme 7)], which is easily accessible
from N-ferrocenylmethyl-N,N,N-trimethylammonium iodide and
O-methylephedrine.32
Sequence 5, R1) CH2NMe2. Next we investigated whether
(Rp)-39, which is easily accessible from (1R,2S,Rp)-28, (R,Rp)-
(33) For an alternative synthesis method see: Widhalm, M.; Nettekoven,
U.; Mereiter, K. Tetrahedron: Asymmetry 1999, 10, 4369-4391.
(34) For alternative synthesis methods see: (a) Refs 12c and 33. (b)
Pickett, T. E.; Roca, F. X.; Richards, C. J. J. Org. Chem. 2003, 68, 2592-
2599.
(35) For an alternative synthesis see: Xiao, L.; Mereiter, K.; Weissen-
steiner, W.; Widhalm, M. Synthesis 1999, 1354-1362.
(36) Tomooka, K. In Chemistry of Organolithium Compounds; Rap-
poport, Z., Marek, I., Eds.; Wiley: Chichester, 2004; pp 749-828.
(31) For the synthesis methodology see: Sˇebesta, R.; Toma, Sˇ; Salisˇova´,
M. Eur. J. Org. Chem. 2002, 692-695.
(32) (a) Xiao, L.; Kitzler, R.; Weissensteiner, W. J. Org. Chem. 2001,
66, 8912-8919. (b) Kitzler, R.; Xiao, L.; Weissensteiner, W. Tetrahe-
dron: Asymmetry 2000, 11, 3459-3462. (c) Fleischer, I.; Toma, Sˇ. Coll.
Czech. Chem. Commun. 2004, 69, 330-338.

Bromide-Mediated ortho-Deprotonation
Organometallics, Vol. 26, No. 15, 2007 3855
Scheme 9
Scheme 10. Synthesis of 1,3-Disubstituted Ferrocenes,
Sequence 5
2032a (Scheme 8), and other sources,35 and its boron complex
(Rp)-40 could be selectively ortho-deprotonated adjacent to the
bromide substituent, since this would provide another route for
the exclusive formation of ferrocene-stereogenic 1,3-disubsti-
tuted derivatives. Furthermore, it was anticipated that the use
of racemic bromide derivative 39, which can be easily obtained
from commercially available N,N-dimethyl-N-ferrocenylmethyl
amine,35,37 would enable the scope of this methodology to be
extended to achiral and racemic 1,3-disubstituted ferrocenes.
In order to ascertain whether ortho-deprotonation next to the
bromide can be carried out selectively in the presence of a
dimethylaminomethyl substituent, rac-39 was reacted under the
conditions optimized for 2 with Li-TMP and DMF as the
electrophile. In this case ortho-lithiation took place next to
bromide as well as adjacent to the dimethylaminomethyl
substituent, and a mixture of aldehydes 41 and 42 in a ratio of
70:30 (84% conversion) was obtained (Scheme 9). For the sake
of better characterization these compounds were reduced with
NaBH4 to the alcohols 43 and 44. We noted with interest that
in a very recent communication Butler and co-workers reported
that the use of modified reaction conditions and Eschenmoser’s
salt as the electrophile gave 1-bromo-2,5-bis(dimethylamino-
methyl)ferrocene from rac-39 in 86% yield.38 We therefore
applied these modified reaction conditions to rac-39, but with
DMF as the electrophile aldehydes 41 and 42 were obtained
only in a slightly better isomer ratio (79:21), albeit with a
decrease in conversion from 84% to 61%. However, treatment
of 39 with BH3(THF) and subsequent reaction of the resulting
boron complex, rac-40, with Li-TMP and different electrophiles
led to exclusive ortho-lithiation adjacent to bromide.
Consequently, for the next reaction sequence boron complex
40 in both its racemic and enantiopure forms was used as the
starting material. In almost all cases identical reaction conditions
were used for the racemic and enantiopure compounds, and
therefore the following discussion concerns only the synthesis
of chiral, nonracemic derivatives (Scheme 10; reaction details
for racemic derivatives are given in the Supporting Information).
Lithiation of (Rp)-40 and further treatment with DMF led to
aldehyde (Sp)-45, which is stable enough for characterization
but on standing at room temperature tends to deprotect to (Sp)-
41 and reacts further on to alcohols 43 and 46. Aldehyde 45
was therefore reduced immediately after workup with BH3(THF)
to alcohol (Sp)-46 (84% based on 40), which on deprotection
with Et2NH gave amino alcohol (Sp)-43 (89%). Optimization
of this reaction sequence allowed the transformation of (Rp)-40
into (Sp)-43 without isolating the intermediates 45 and 46 and
gave an overall yield of 87%. Finally, when 43 was reacted
with n-BuLi and H2O, the 1,3-disubstituted ferrocene (Rp)-52
(93%) was obtained.39 In a similar way to 43, compound 46
can also be debrominated with n-BuLi and H2O, which leads
to the 1,3-disubstituted boron complex (Rp)-49 (93%). Decom-
plexation of this derivative with Et2NH also resulted in amino
alcohol (Rp)-52 (93%).
In this sequence, CO2 was tested as the electrophile in addition
to DMF. Reaction of (Rp)-40 with Li-TMP and CO2 gave the
very stable carbonic acid (Sp)-47 (89%), which when treated
with a solution of CH2N2 in diethyl ether, resulted in the methyl
ester (Sp)-48 (80%). A search for a suitable debromination
method revealed that hydrogenation under basic conditions with
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base and Pd
on charcoal as the catalyst was best suited. The use of these
conditions led to debromination of 48 and, at the same time,
deprotection to the 1,3-disubstituted ester (Rp)-53 in 89% yield.40
Furthermore, carbonic acid 47 reacted with n-BuLi (2.2 equiv)
and H2O to give the 1,3-disubstituted boron complex (Rp)-50
(91%), which was reacted with CH2N2 in diethyl ether to give
ester (Rp)-51 quantitatively.
In this case the pincer ligand (Rp)-54, which bears a pyrazole
substituent, was prepared in one step from (Rp)-52 (54%).31
Overall, depending on whether starting material 39 is used
in its racemic or enantiopure form, this sequence provides easy
access to achiral, racemic and chiral, nonracemic 1,2,3-tri- and
1,3-disubstituted ferrocene derivatives. Under optimized condi-
tions, 1,3-disubstituted amino alcohol (Rp)-52 was prepared from
(Rp)-39 in 79% overall yield without isolating intermediates 45
and 46.
Concluding Remarks
In this study we have evaluated five bromide-mediated
reaction sequences for the synthesis of 1,2,3-tri- and 1,3-
(39) For rac-52 see also: Koridze A. A.; Sheloumov, A. M.; Kuklin, S.
A.; Lagunova, V. Y.; Petukhova, I. I.; Dolgushin, F. M.; Ezernitskaya, M.
G.; Petrovskii, P. V.; Macharashvili, A. A.; Chedia, R. V. Russ. Chem.
Bull. 2002, 51, 1077-1078.
(40) For an analogous procedure see: Sajiki, H.; Kume, A.; Hattori, K.;
Hirota, K. Tetrahedron Lett. 2002, 43, 7247-7250.
(37) Marr, G.; Moore, R. E.; Rockett, B. W. J. Chem. Soc. (C) 1968,
24-27.
(38) Butler, I. R.; Woldt, B.; Oh, M.-Z.; Williams, D. J. Inorg. Chem.
Commun. 2006, 9, 1255-1258.

3856 Organometallics, Vol. 26, No. 15, 2007
Steurer et al.
4.25 (s, 5H, Cp′), 4.61 (d, J ) 2.8 Hz, 1H, Cp-H4), 4.90 (d, J )
2.8 Hz, 1H, Cp-H3), 10.22 (s, 1H, CHO). 13C NMR (100 MHz,
CDCl3): δ 15.8 (CH3CH), 41.0 (2C, N(CH3)2), 55.7 (CHCH3), 65.6
(Cp-C3), 69.6 (Cp-C4), 72.8 (5C, Cp′), 75.3, 92.9 (2 Cp-Cq), 193.9
(CHO), 1 Cp-Cq not observed. MS (60 °C) m/z (%): 365/363 (30)
[M+], 321/319 (6), 268 (28), 239 (54), 212 (16). HRMS: calcd for
disubstituted ferrocenes. All sequences start from a monosub-
stituted ferrocene derivative Fc-R1, bearing either a stereogenic
or a nonstereogenic ortho-directing group (R1), and involve two
consecutive ortho-deprotonation steps. In the first step, 2-bromo-
substituted derivatives (1-R1,2-Br-Fc) are prepared, while in the
second step the use of Li-TMP as the base enables deprotonation
of the position adjacent to the bromo substituent. The use of
appropriate electrophiles provides access to a variety of 1,2,3-
trisubstituted ferrocenes (1-R1,2-Br,3-R3-Fc) using these routes.
In some cases, in order to prevent interference of ortho-directing
groups R1 in the second deprotonation step, these groups had
to be transformed into nondirecting substituents. This could,
for example, be achieved by transforming amino functionalities
(R1) into their amine-trihydroboron complexes.
Since bromide can be easily removed from trisubstituted
ferrocenes (1-R1,2-Br,3-R3-Fc) either by bromide-lithium
exchange or by catalytic hydrogenation, 1,3-disubstituted fer-
rocene derivatives (1-R1,3-R3-Fc) become accessible in high
overall yield, and this includes pincer-type derivatives.
In general, (i) bromide as an ortho-directing group can be
used in combination with a number of stereogenic and non-
stereogenic functional groups, (ii) with Li-TMP as the base
ortho-deprotonation next to bromide can be achieved in high
yield and in most cases with very high stereoselectivity, and
(iii) bromide can be easily exchanged by other electrophiles.
20
C15H18BrFeNO 362.9923, found 362.9928. [R]λ (nm): -720
(589), -806 (578), -1334 (546) (c 0.128, CHCl3).
(R,Rp)-1-Bromo-5-[1-(N,N-dimethylamino)ethyl]-2-hydroxy-
methylferrocene, (R,Rp)-5. A suspension of LiAlH4 (35 mg, 0.923
mmol) in THF (3 mL) was flushed with Ar and cooled to 0 °C
before a degassed solution of (R,Rp)-4 (261 mg, 0.717 mmol) in
THF (5 mL) was added dropwise at 0 °C. The reaction mixture
was subsequently stirred for 30 min at 0 °C followed by 16 h at rt.
The reaction was cooled to 0 °C and then quenched with ethanol
(10 mL) followed by water (20 mL). Diethyl ether was added, and
the phases were separated. The aqueous phase was extracted three
times with diethyl ether. The organic phases were combined and
washed with brine. After drying over MgSO4 and removal of the
solvents under reduced pressure, the residue was chromatographed
on alumina. A mixture of petroleum ether, ethyl acetate, and
triethylamine (30:30:1) eluted nonpolar impurities, while ethanol
eluted product (R,Rp)-5 (241 mg, 0.658 mmol, 92% yield, yellow
powder).
1
Mp: 139-146 °C. H NMR (400 MHz, CDCl3): δ 1.50 (d, J
) 6.9 Hz, 3H, CHCH3), 1.74 (br s, 1H, OH), 2.15 (s, 6H, N(CH3)2),
3.78 (q, J ) 6.9 Hz, 1H, CHCH3), 4.13 (s, 5H, Cp′), 4.15 (d, J )
2.8 Hz, 1H, Cp-H4), 4.31 (d, J ) 2.8 Hz, 1H, Cp-H3), 4.45, 4.46
(AB, J ) 12.4 Hz, 2H, CH2). 13C NMR (100 MHz, CDCl3): δ
15.9 (CH3CH), 41.0 (2C, N(CH3)2), 56.3 (CHCH3), 60.2 (CH2),
64.9 (Cp-C4), 65.9 (Cp-C3), 71.6 (5C, Cp′), 81.6, 85.2, 88.4 (3
Cp-Cq). MS (80 °C) m/z (%): 367/365 (77) [M+], 352/350 (9),
323/321 (41), 296/295 (21), 214/212 (37), 121 (18). HRMS: calcd
for C15H20BrFeNO 365.0079, found 365.0085. [R]λ20 (nm): +16.7
(589), +18.4 (578), +28.8 (546) (c 0.576, CHCl3).
Experimental Section
General Methods. Melting points were determined on a Kofler
1
melting point apparatus and are uncorrected. H (400.132 MHz),
13C NMR (100.624 MHz), and 31P (161.975 MHz) spectra were
recorded in CDCl3. Chemical shifts (δ) are reported in ppm relative
to CHCl3 (7.26, 1H), CDCl3 (77.0, 13C), and 85% H3PO4 (0.0, 31P).
1
In H NMR data br s, d, t, and q refer to broad singlet, doublet,
triplet, and quartet, respectively, and Cq in 13C NMR data stands
for quaternary carbon atom. Mass spectra were measured on a
Finnigan MAT 900S or Finnigan MAT 8230 (EI, 70 eV) spec-
trometer. Optical rotations were measured on a Perkin-Elmer 241
polarimeter at 20 °C. All reactions were carried out under Ar using
standard Schlenk techniques. Pentane and Et2O were distilled from
lithium aluminum hydride, acetonitrile and dichloromethane were
distilled from calcium hydride, and THF was distilled from sodium
and benzophenone under Ar prior to use. Acetic acid and acetic
anhydride were freshly distilled, and Ar was bubbled through each
for 12 h prior to use. Chromatographic separations were performed
under gravity on either silica gel (Merck, 40-63 µm) or alumina
(Merck, aluminum oxide 90, 0.063-0.200 mm). Petroleum ether
with a boiling range of 55-65 °C was used for chromatography.
Typical Procedures. (R,Rp)-1-Bromo-5-[1-(N,N-dimethylami-
no)ethyl]-2-formylferrocene, (R,Rp)-4. To a degassed solution of
(R,Sp)-225a (500 mg, 1.488 mmol) in THF (5 mL) was added
dropwise at -78 °C Li-TMP in THF/hexane (0.7 M, 4.25 mL, 2.98
mmol). The reaction mixture was subsequently stirred for 30 min
at -78 °C followed by 3 h at -30 °C. The temperature was again
lowered to -78 °C, and dimethylformamide (350 µL, 4.52 mmol)
was added. The temperature was raised to 0 °C, and stirring was
continued for 16 h. The reaction was quenched with saturated
aqueous Na2CO3 (15 mL) before diethyl ether was added, and the
phases were separated. The aqueous phase was extracted three times
with diethyl ether. The combined organic phases were washed with
brine. After drying over MgSO4 and removal of the solvents under
reduced pressure, the residue was chromatographed on alumina. A
mixture of petroleum ether, ethyl acetate, and triethylamine in a
ratio of 30:10:1 eluted (R,Rp)-4 (442 mg, 1.214 mmol, 82% yield)
as a red oil.
(R,Sp)-3-[1-(N,N-Dimethylamino)ethyl]-1-hydroxymethylfer-
rocene, (R,Sp)-8. To a degassed solution of (R,Rp)-5 (70 mg, 0.191
mmol) in THF (3 mL) was added dropwise at -78 °C n-BuLi in
hexane (1.6 M, 300 µL, 0.48 mmol). After stirring for 30 min at
0 °C the reaction was quenched with water (10 mL) before diethyl
ether was added, and the phases were separated. The aqueous phase
was extracted three times with diethyl ether. The organic phases
were combined and washed with brine. After drying over MgSO4
and removal of the solvents under reduced pressure, the residue
was chromatographed on alumina. A mixture of petroleum ether,
ethyl acetate, and triethylamine (30:30:1) eluted nonpolar impurities,
while ethanol eluted product (R,Sp)-8 (48 mg, 0.167 mmol, 88%
yield, yellow powder).
Crystals for the X-ray structure determination were grown by
crystallization from dichloromethane/petroleum ether.
1
Mp: 113-117 °C. H NMR (400 MHz, CDCl3): δ 1.42 (d, J
) 6.9 Hz, 3H, CHCH3), 1.71 (br s, 1H, OH), 2.09 (s, 6H, N(CH3)2),
3.57 (q, J ) 6.9 Hz, 1H, CHCH3), 4.11 (m, 1H, Cp-H), 4.12 (s,
5H, Cp′), 4.21 (m, 1H, Cp-H), 4.25 (t, J ) 1.4 Hz, 1H, Cp-H2),
4.33 (s, 2H, CH2OH). 13C NMR (100 MHz, CDCl3): δ 15.6
(CHCH3), 40.6 (2C, N(CH3)2), 58.5 (CHCH3), 60.9 (CH2OH), 66.96
(Cp-CH), 66.99 (Cp-CH), 69.0 (5C, Cp′), 69.1 (Cp-C2), 87.8, 87.9
(2 Cp-Cq). MS (70 °C) m/z (%): 287 (81) [M+], 272 (25), 243
(90), 225 (27), 134 (100). HRMS: calcd for C15H21FeNO 287.0973,
found 287.0980. [R]λ20 (nm): -1.2 (589), -1.6 (578), -7.9 (546)
(c 0.674, CHCl3).
(R,Rp)-1-Bromo-2-[(2-methoxymethylpyrrolidin-1-yl)methyl]-
ferrocene, (R,Rp)-20. To a degassed solution of (R)-N-ferrocenyl-
methyl-2-methoxymethylpyrrolidine, (R)-1929 (2 g, 6.385 mmol),
in diethyl ether (32 mL) was added dropwise at -78 °C s-BuLi in
cyclohexane (1.3 M, 5.9 mL, 7.67 mmol). The reaction mixture
was stirred for 1.5 h at -78 °C and 1.5 h at -30 °C before the
1H NMR (400 MHz, CDCl3): δ 1.47 (d, J ) 6.9 Hz, 3H,
CHCH3), 2.17 (s, 6H, N(CH3)2), 3.87 (q, J ) 6.9 Hz, 1H, CHCH3),

Bromide-Mediated ortho-Deprotonation
Organometallics, Vol. 26, No. 15, 2007 3857
temperature was lowered to -78 °C, and a degassed solution of
Br2CHCHBr2 (6.22 g, 23.94 mmol) in diethyl ether (20 mL) was
added dropwise within 30 min. Stirring was continued for an
additional 30 min at -78 °C and 16 h at rt. The reaction was
quenched with water (20 mL), and the phases were separated. The
aqueous phase was extracted with dichloromethane (3 × 10 mL),
and the organic phases were combined and washed with an aqueous
solution of Na2S2O5, NaOH (0.05 M), and brine. The organic phases
were extracted with an aqueous solution of citric acid (10%, 3 ×
50 mL), and the combined aqueous phases were extracted with
diethyl ether (3 × 30 mL). The aqueous phases were basified at
0 °C with NaOH (2 M, pH 9) and subsequently extracted with
diethyl ether. After drying over MgSO4 and removal of the solvents
under reduced pressure, the residue was chromatographed on
alumina. A mixture of petroleum ether, diethyl ether, and triethyl-
amine (80:20:1) was used as the eluent to give (R,Rp)-20 (1.85 g,
4.718 mmol, 74% yield) as a dark orange oil.
1H NMR (400 MHz, CDCl3): δ 1.54-1.78 (m, 3H, NCH2CH2
+ NCHCHH), 1.80-1.91 (m, 1H, NCHCHH), 2.21-2.31 (m, 1H,
NCHHCH2), 2.69-2.78 (m, 1H, NCHCH2), 2.99-3.01 (m, 1H,
NCHHCH2), 3.25, 3.44 (AB-part of an ABX system, JAB ) 9.3
Hz, JAX ) 6.3 Hz, JBX ) 4.8 Hz, 2H, CHCH2OCH3), 3.36 (s, 3H,
OCH3), 3.47, 3.98 (AB, J ) 13.4 Hz, 2H, CpCH2N), 4.08 (t, J )
2.5 Hz, 1H, Cp-H4), 4.14 (s, 5H, Cp′), 4.20-4.23 (m, 1H, Cp-
H3), 4.39-4.42 (m, 1H, Cp-H5). 13C NMR (100 MHz, CDCl3): δ
22.8 (NCH2CH2), 28.6 (NCHCH2), 52.0 (CpCH2N), 54.4 (NCH2-
CH2), 59.1 (OCH3), 61.9 (NCHCH2), 66.2 (Cp-C4), 68.3 (Cp-C3),
70.2 (Cp-C5), 71.02 (5C, Cp′), 71.03 (Cp-Cq), 76.5 (CHCH2OCH3)
80.8 (Cp-Cq). MS (100 °C) m/z (%): 393/391 (8) [M+], 348/346
(7), 294/292 (27), 279/277 (48), 212 (56), 184 (24), 128 (57), 84
(23), 56 (100). HRMS: calcd for C17H22BrFeNO 391.0236, found
391.0230. [R]λ20 (nm): +28.8 (589), +27.7 (578), +17.8 (546) (c
0.534, CHCl3).
and 1 h at 0 °C. The reaction was quenched with water (1 mL),
and diethyl ether was added. The phases were separated, and the
aqueous phase was extracted three times with diethyl ether. The
organic phases were combined and washed with brine. After drying
over MgSO4 and removal of the solvents under reduced pressure,
the residue was dissolved in ethanol (15 mL). To this solution was
added at rt NaBH4 (140 mg, 3.70 mmol) in three portions, and the
resulting mixture was stirred for 16 h at rt. The reaction was
quenched with water (10 mL), and ethanol was removed under
reduced pressure. The aqueous phase was extracted with dichlo-
romethane (3 × 5 mL), and the combined organic phases were
washed with brine. After drying over MgSO4 and removal of the
solvents under reduced pressure, the residue was dissolved in
diethylamine and stirred for 16 h at rt. Diethylamine was removed
under reduced pressure immediately before the residue was purified
by chromatography on alumina. A mixture of petroleum ether and
ethyl acetate (5:1) removed a mixture of byproducts, while
petroleum ether and ethyl acetate (3:1) eluted (R,Sp)-24 (869 mg,
0.206 mmol, 84% yield) as an orange oil.
1H NMR (400 MHz, CDCl3): δ 1.54-1.77 (m, 4H, NCH2CH2
+ NCHCHH + OH), 1.81-1.92 (m, 1H, NCHCHH), 2.20-2.30
(m, 1H, NCHHCH2), 2.69-2.77 (m, 1H, NCHCH2), 3.01-3.07
(m, 1H, NCHHCH2), 3.29, 3.47 (AB-part of an ABX system, JAB
) 9.4 Hz, JAX ) 6.1 Hz, JBX ) 4.8 Hz, 2H, CHCH2OCH3), 3.37
(s, 3H, OCH3), 3.43, 4.02 (AB, J ) 13.4 Hz, 2H, CpCH2N), 4.12
(s, 5H, Cp′), 4.26 (s, 2H, 2 Cp-H), 4.40, 4.57 (AB, J ) 12.3 Hz,
2H, CpCH2OH). 13C NMR (100 MHz, CDCl3): δ 22.7 (NCH2CH2),
28.5 (NCHCH2), 52.1 (CpCH2N), 54.4 (NCH2CH2), 59.2 (OCH3),
60.1 (CpCH2OH), 62.1 (NCHCH2), 66.4, 68.0 (2 Cp-CH), 71.4 (5C,
Cp′), 76.6 (CHCH2O), 82.6, 83.7, 85.9 (3 Cp-Cq). MS (90 °C) m/z
(%): 423/421 (4) [M+], 378/376 (5), 309/307 (96), 171/169 (24),
155 (100), 138 (24), 121 (17). HRMS: calcd for C18H24BrFeNO2
421.0342, found 421.0350. [R]λ20 (nm): +34.6 (589), +34.4 (578),
+30.7 (546) (c 0.596, CHCl3).
(R,Rp)-1-Hydroxymethyl-3-[(2-methoxymethylpyrrolidin-1-
yl)methyl]ferrocene, (R,Rp)-25. To a degassed solution of (R,Sp)-
24 (700 mg, 1.658 mmol) in THF (2 mL) was added dropwise at
-78 °C n-BuLi in hexane (1.6 M, 2.6 mL, 4.16 mmol). After
stirring for 1 h at 0 °C the reaction was quenched with water
(10 mL). Diethyl ether was added, and the phases were separated.
The aqueous phase was extracted three times with diethyl ether.
The organic phases were combined and washed with brine. After
drying over MgSO4 and removal of the solvents under reduced
pressure, the residue was chromatographed on alumina. A mixture
of petroleum ether and ethyl acetate (1:1) eluted starting material,
while elution with petroleum ether, ethyl acetate, and ethanol (15:
30:1) gave product (R,Rp)-25 (500 mg, 1.457 mmol, 88% yield) as
an orange oil.
1H NMR (400 MHz, CDCl3): δ 1.44-1.68 (m, 3H, NCH2CH2
+ NCHCHH), 1.70-1.82 (m, 1H, NCHCHH), 2.12-2.22 (m, 1H,
NCHHCH2), 2.53-2.61 (m, 1H, NCHCH2), 2.72 (br s, 1H, OH),
2.81-2.89 (m, 1H, NCHHCH2), 3.20, 3.32 (AB-part of an ABX
system, JAB ) 9.4 Hz, JAX ) 6.0 Hz, JBX ) 5.0 Hz, 2H, CHCH2-
OCH3), 3.27, 3.68 (AB, J ) 13.1 Hz, 2H, CpCH2N), 3.30 (s, 3H,
OCH3), 4.05 (s, 5H, Cp′), 4.07-4.12 (s, 2H, 2 Cp-H), 4.21 (br s,
3H, Cp-H + CH2OH). 13C NMR (100 MHz, CDCl3): δ 22.4
(NCH2CH2), 28.3 (NCHCH2), 53.6 (CpCH2N), 53.9 (NCH2CH2),
58.9 (OCH3), 60.3 (CpCH2OH), 61.5 (NCHCH2), 67.6 (Cp-CH),
68.6 (5C, Cp′), 69.9 (Cp-CH), 70.0 (Cp-CH), 76.1 (CHCH2O), 83.8,
88.1 (2 Cp-Cq). MS (80 °C) m/z (%): 343 (24) [M+], 229 (100),
211 (14), 135 (10), 91 (39). HRMS: calcd for C18H25FeNO2
343.1235, found 343.1241. [R]λ20 (nm): +63.0 (589), +64.5 (578),
+67.8 (546) (c 1.066, CHCl3).
{(R,Rp)-1-Bromo-2-[(2-methoxymethylpyrrolidin-1-yl)methyl]-
ferrocene}trihydroboron, (R,Rp)-23. To a degassed solution of
(R,Rp)-20 (1 g, 2.55 mmol) in THF (13 mL) was added dropwise
at 0 °C BH3(THF) in THF (1.0 M, 7.6 mL, 7.6 mmol). The reaction
mixture was subsequently stirred for 3 h at rt. The reaction was
quenched with water (20 mL), and diethyl ether was added. The
phases were separated, and the aqueous phase was extracted three
times with diethyl ether. The organic phases were combined and
washed with brine. After drying over MgSO4 and removal of the
solvents under reduced pressure (R,Rp)-23 (1.05 g, 95% chemical
purity as determined by 1H NMR) was obtained as a highly viscous
orange oil. Since (R,Rp)-23 tends to deprotect on chromatography,
it was used without further purification.
1H NMR (400 MHz, CDCl3): δ 1.4-1.8 (br s, 3H, BH3), 1.73-
1.83 (m, 3H, NCH2CH2 + NCHCHH), 2.03-2.14 (m, 1H,
NCHCHH), 2.58-2.68 (m, 1H, NCHHCH2), 3.05-3.12 (m, 1H,
NCHHCH2), 3.13-3.22 (m, 1H, NCHCH2), 3.43 (s, 3H, OCH3),
3.48, 4.02 (AB-part of an ABX system, JAB ) 10.2 Hz, JAX ) 4.3
Hz, JBX ) 7.6 Hz, 2H, CHCH2OCH3), 4.19, 4.44 (AB, J ) 14.4
Hz, 2H, CpCH2N), 4.19 (s, 5H, Cp′), 4.21 (t, J ) 2.6 Hz, 1H, Cp-
H4), 4.51 (dd, J1 ) 2.6 Hz, J2 ) 1.5 Hz, 1H, Cp-H), 4.57 (dd, J1
) 2.6 Hz, J2 ) 1.5 Hz, 1H, Cp-H). 13C NMR (100 MHz, CDCl3):
δ 19.8 (NCH2CH2), 25.7 (NCHCH2), 57.2 (CpCH2N), 59.1 (OCH3),
59.5 (NCH2CH2), 62.8 (NCHCH2), 67.7 (Cp-CH), 71.4 (2 Cp-CH),
71.6 (5C, Cp′), 72.3 (CHCH2OCH3), 82.4 (Cp-Cq), 1 Cp-Cq not
observed.
(R,Sp)-1-Bromo-2-hydroxymethyl-5-[(2-methoxymethylpyrro-
lidin-1-yl)methyl]ferrocene, (R,Sp)-24. To a degassed solution of
(R,Rp)-23 (1 g, 2.46 mmol) in THF (12 mL) was added dropwise
at -78 °C Li-TMP in THF/hexane (0.7 M, 7.0 mL, 4.9 mmol).
The reaction mixture was stirred for 30 min at -78 °C and 3 h at
-30 °C. After lowering the temperature again to -78 °C dimeth-
ylformamide (570 µL, 7.36 mmol) was added dropwise, and the
reaction mixture was subsequently stirred for 30 min at -78 °C
(R,Rp)-1-[(Pyrazol-1-yl)methyl]-3-[(2-methoxymethylpyrroli-
din-1-yl)methyl]ferrocene, (R,Rp)-26. To a degassed solution of
(R,Rp)-25 (250 mg, 0.728 mmol) and sodium iodide (220 mg, 1.47
mmol) in acetonitrile (10 mL) was added dropwise at rt chloro-

3858 Organometallics, Vol. 26, No. 15, 2007
Steurer et al.
trimethylsilane (230 µL, 1.80 mmol). The resulting suspension was
stirred for 5 min before pyrazole (139 mg, 2.04 mmol) was added.
After stirring the reaction mixture at rt for 16 h, water (10 mL)
was added and the pH was adjusted with aqueous NaOH to about
10. The aqueous phase was extracted with dichloromethane (3 ×
20 mL), and the combined organic phases were washed with brine
and dried over MgSO4. The solvents were removed under reduced
pressure, and the residue was purified by chromatography. A
mixture of petroleum ether and ethyl acetate in a ratio of 1:1 eluted
byproducts, while elution with petroleum ether, ethyl acetate, and
ethanol (45:45:10) gave product (R,Rp)-26 (213 mg, 0.542 mmol,
74% yield) as an orange oil.
1H NMR (400 MHz, CDCl3): δ 1.52-1.73 (m, 3H, NCH2CH2
+ NCHCHH), 1.78-1.89 (m, 1H, NCHCHH), 2.17-2.26 (m, 1H,
NCHHCH2), 2.57-2.65 (m, 1H, NCHCH2), 2.91-2.97 (m, 1H,
NCHHCH2), 3.22, 3.32 (AB-part of an ABX system, JAB ) 9.3
Hz, JAX ) 6.3 Hz, JBX ) 5.2 Hz, 2H, CHCH2OCH3), 3.30 (s, 3H,
OCH3), 3.34, 3.72 (AB, J ) 13.4 Hz, 2H, Cp(C3)CH2N), 4.10 (s,
5H, Cp′), 4.18-4.20 (m, 1H, Cp-H4), 4.20-4.22 (m, 1H, Cp-H5),
4.32 (br t, 1H, Cp-H2), 5.00, 5.04 (AB, J ) 14.4 Hz, 2H, Cp-
(C1)CH2N), 6.21 (dd, J1 ) J2 ) 2.0 Hz, 1H, NNCHCH), 7.34 (d,
J ) 2.0 Hz, 1H, NNCHCHCH), 7.48 (d, J ) 2.0 Hz, 1H, NNCH).
13C NMR (100 MHz, CDCl3): δ 22.7 (NCH2CH2), 28.5 (NCHCH2),
51.6 (Cp(C1)CH2N), 54.1 (Cp(C3)CH2N), 54.5 (NCH2CH2), 59.1
(OCH3), 62.1 (NCHCH2), 68.7 (Cp-C5), 69.3 (5C, Cp′), 70.5 (Cp-
C4), 70.9 (Cp-C2), 76.4 (CHCH2O), 83.0 (Cp-Cq), 105.3 (NNCHCH),
128.3 (NNCHCHCH), 138.8 (NNCH), 1 Cp-Cq not observed. MS
(80 °C) m/z (%): 393 (10) [M+], 279 (100), 236 (34), 211 (46),
121 (32), 91 (43). HRMS: calcd for C21H27FeN3O 393.1504, found
393.1512. [R]λ20 (nm): +44.3 (589), +45.1 (578), +46.5 (546) (c
0.548, CHCl3).
4.11 (s, 5H, Cp′), 4.27 (d, J ) 2.8 Hz, 1H, Cp-H4), 4.29 (d, J )
2.8 Hz, 1H, Cp-H3), 4.41, 4.58 (AB, J ) 12.4 Hz, 2H, CH2OH).
13C NMR (100 MHz, CDCl3): δ 45.0 (2C, N(CH3)2), 57.1 (CH2N-
(CH3)2), 60.0 (CH2OH), 66.7 (Cp-C3), 68.0 (Cp-C4), 71.4 (5C,
Cp’), 82.6, 83.0, 85.9 (3 Cp-Cq). MS (30 °C) m/z (%): 353/351
(40) [M+], 309/307 (10), 155 (41), 134 (33), 84 (100). HRMS:
20
calcd for C14H18BrFeNO 350.9923, found 350.9945. [R]λ (nm):
-35.7 (589), -38.1 (578), -52.5 (546) (c 0.465, CHCl3).
(Sp)-[1-Bromo-2-hydroxycarbonyl-5-(N,N-dimethylamino)-
methylferrocene]trihydroboron, (Sp)-47. To a degassed solution
of (Rp)-40 (1 g, 2.977 mmol) in THF (30 mL) was added dropwise
at -78 °C Li-TMP in THF/hexane (0.7 M, 5.1 mL, 3.57 mmol).
The reaction mixture was stirred for 30 min at -78 °C and 3 h at
-30 °C. The reaction mixture was poured on ground dry ice
(30 g) and stirred for 1 h. To this solution was added water
(70 mL) and ethyl acetate (100 mL). The phases were separated,
and the organic phase was extracted with water. The combined
aqueous phases were extracted once with diethyl ether (50 mL)
and were acidified with H3PO4 (50%) to pH 4. The aqueous phase
was extracted with dichloromethane (4 × 50 mL), and the combined
dichloromethane phases were washed once with brine (30 mL) and
were dried over MgSO4. Removal of the solvents under reduced
pressure afforded crude (Sp)-47 (1.007 g, 2.65 mmol, 89% yield)
as a glassy yellow powder, which was used without further
purification.
1H NMR (400 MHz, CDCl3): δ 1.4-2.2 (br s, 3H, BH3), 2.51
(s, 3H, N(CH3)2-A), 2.57 (s, 3H, N(CH3)2-B), 3.92, 4.22 (AB, J )
14.1 Hz, 2H, CH2), 4.30 (s, 5H, Cp′), 4.77 (d, J ) 2.9 Hz, 1H,
Cp-H4), 5.04 (d, J ) 2.8 Hz, 1H, Cp-H3), COOH not observed.
13C NMR (100 MHz, CDCl3): δ 49.7 (N(CH3)2-A), 50.9 (N(CH3)2-
B), 61.2 (CH2), 71.0 (Cp-C3), 73.3 (Cp-C4), 73.7 (5C, Cp′), 62.2,
81.3, 81.7 (3 Cp-Cq), 175.2 (COOH). MS (80 °C) m/z (%): 381/
379 (35) [M+], 367/365 (35), 323/321 (15), 255 (27), 241 (23),
169 (38), 57 (100). HRMS: calcd for C14H19BBrFeNO2 379.0046,
(Sp)-1-Bromo-2-hydroxymethyl-5-(N,N-dimethylamino)meth-
ylferrocene, (Sp)-43. From 40: To a degassed solution of (Rp)-40
(750 mg, 2.233 mmol) in THF (15 mL) was added dropwise at
-78 °C Li-TMP in THF/hexane (0.7 M, 6.4 mL, 4.48 mmol). The
reaction mixture was stirred for 30 min at -78 °C and 3 h at
-30 °C. After lowering the temperature again to -78 °C dimeth-
ylformamide (520 µL, 6.7 mmol) was added dropwise, and the
reaction mixture was subsequently stirred for 30 min at -78 °C
and 30 min at 0 °C. The reaction was quenched with water
(15 mL) before diethyl ether was added. The phases were separated,
and the aqueous phase was extracted three times with diethyl ether.
The organic phases were combined and washed with brine. After
drying over MgSO4 and removal of the solvents under reduced
pressure, the residue was dissolved in ethanol (15 mL) and NaBH4
(125 mg, 3.30 mmol) was added at rt. After stirring for 16 h at rt,
water (15 mL) was added and ethanol was removed under reduced
pressure. The remaining aqueous phase was extracted with diethyl
ether (3 ×), the combined organic phases were dried over MgSO4,
and the solvents were removed under reduced pressure. The residue
was dissolved in diethylamine (10 mL), and the solution was stirred
for 16 h at rt. Diethylamine was removed under reduced pressure,
and immediately afterward the residue was purified by chroma-
tography on alumina. A mixture of petroleum ether and ethyl acetate
(5:1) followed by a mixture of petroleum ether, ethyl acetate, and
ethanol (15:5:1) eluted product (Sp)-43 (681 mg, 1.934 mmol, 87%
yield) as an orange oil.
20
found 378.9885. [R]λ (nm): -4.2 (589), -3.4 (578) (c 0.377,
CHCl3).
(Sp)-[1-Bromo-2-methoxycarbonyl-5-(N,N-dimethylamino)-
methylferrocene]trihydroboron, (Sp)-48. To a solution of (Sp)-
47 (503 mg, 1.324 mmol) in dichloromethane (20 mL) and methanol
(2 mL) was added at rt a solution of CH2N2 in diethyl ether (1 M,
2.5 mL, 2.5 mmol), and stirring was continued for 30 min. The
solvents were removed under reduced pressure, and the residue was
purified by chromatography on alumina. A mixture of petroleum
ether and ethyl acetate (7:3) as the eluent afforded (Sp)-48 (418
mg, 1.061 mmol, 80% yield) as a yellow solid.
1
Mp: 145-148 °C. H NMR (400 MHz, CDCl3): δ 1.35-2.20
(br s, 3H, BH3), 2.49 (s, 3H, N(CH3)2-A), 2.54 (s, 3H, N(CH3)2-
B), 3.88 (s, 3H, OCH3), 3.90, 4.21 (AB, J ) 14.0 Hz, 2H, CH2),
4.24 (s, 5H, Cp’), 4.70 (d, J ) 2.9 Hz, 1H, Cp-H4), 4.94 (d, J )
2.9 Hz, 1H, Cp-H3). 13C NMR (100 MHz, CDCl3): δ 49.6
(N(CH3)2-A), 50.8 (N(CH3)2-B), 51.9 (OCH3), 61.2 (CH2), 70.4
(Cp-C3), 72.6 (Cp-C4), 73.3 (5C, Cp′), 80.5, 81.4 (2 Cp-Cq), 1
Cp-Cq + CO-Cq not observed. MS (80 °C) m/z (%): 393/395 (12)
[M+], 381/379 (35), 367/365 (35), 323/321 (15), 255 (27), 241 (23),
169 (38), 57 (100). HRMS: calcd for C15H21BBrFeNO2 393.0203,
found 393.0185. [R]λ20 (nm): -2.2 (589), -0.2 (578), +4.2 (546)
(c 0.499, CHCl3).
From 46: A solution of (Sp)-46 (1.638 g, 4.477 mmol) in
diethylamine (40 mL) was stirred at rt for 16 h. Diethylamine was
removed under reduced pressure, and immediately afterward the
residue was purified by chromatography on alumina. A mixture of
petroleum ether and ethyl acetate in a ratio of 1:1 followed by a
mixture of petroleum ether, ethyl acetate, and triethylamine (50:
50:1) eluted product (Sp)-43 (1.40 g, 3.977 mmol, 89% yield) as
an orange oil.
(Rp)-1-Methoxycarbonyl-3-(N,N-dimethylamino)methylfer-
rocene, (Rp)-53. To a solution of (Sp)-48 (297 mg, 0.754 mmol) in
methanol (60 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU, 420 µL, 2.87 mmol) and palladium on charcoal (10%, 0.015
mmol). The resulting suspension was hydrogenated in a Parr
apparatus for 24 h at rt at a hydrogen pressure of 50 psi (3.45 bar).
The suspension was flushed with argon, the catalyst was filtered
off, and the solvent was removed under reduced pressure. The
residue was purified by chromatography on alumina. Ethyl acetate
1H NMR (400 MHz, CDCl3): δ 1.89 (br s, 1H, OH), 2.23 (s,
6H, N(CH3)2), 3.36, 3.48 (AB, J ) 13.1 Hz, 2H, CH2N(CH3)2),

Bromide-Mediated ortho-Deprotonation
Organometallics, Vol. 26, No. 15, 2007 3859
as the eluent afforded (Rp)-53 (201 mg, 0.667 mmol, 89% yield)
of the reciprocal space with θmax ) 30°. After data integration with
the program SAINT+, corrections for absorption, λ/2 effects, and
crystal decay were applied with the program SADABS.41 The
structure was solved by direct methods and refined on F2 with the
program suite SHELX97.42 All non-hydrogen atoms were refined
anisotropically. Most H atoms were placed in calculated positions
and thereafter treated as riding. Crystal data: C15H21FeNO, Mr )
287.18, orthorhombic, space group P212121 (no. 19), T ) 173(2)
K, a ) 6.2478(4) Å, b ) 10.4688(6) Å, c ) 20.7139(12) Å, V )
1354.83(14) Å3, Z ) 4, µ ) 1.101 mm-1. Of 17 488 reflections
collected, 3921 were independent; final R indices: R1 ) 0.0208
(all data), wR1 ) 0.0533 (all data). A view of the molecular structure
with selected bond distances is shown in Figure 1. The O-H group
donates a hydrogen bond to the amino nitrogen, O-N ) 2.877(1)
Å, thereby linking the molecules to give discrete chains parallel to
the b-axis.
as a yellow solid.
Mp: 52-57 °C. H NMR (400 MHz, CDCl3): δ 2.18 (s, 6H,
1
N(CH3)2), 3.25, 3.30 (AB, J ) 12.9 Hz, 2H, CH2), 3.79 (s, 3H,
OCH3), 4.16 (s, 5H, Cp′), 4.41 (dd, J1 ) 2.4 Hz, J2 ) 1.3 Hz, 1H,
Cp-H4), 4.77 (dd, J1 ) 2.4 Hz, J2 ) 1.3 Hz, 1H, Cp-H5), 4.82 (br
t, J ) 1.3 Hz, 1H, Cp-H2). 13C NMR (100 MHz, CDCl3) δ 44.8
(2C, N(CH3)2), 51.5 (OCH3), 58.8 (CH2), 70.1 (Cp-C5), 70.2 (5C,
Cp′), 72.0 (Cp-C2), 73.1 (Cp-C4), 70.9, 86.9 (2 Cp-Cq), 172.1 (CO-
Cq). MS (50 °C) m/z (%): 301 (100) [M+] 257 (83), 242 (32), 199
(20), 148 (33), 121 (45), 105 (69). HRMS: calcd for C15H19FeNO2
20
301.0765, found 301.0769. [R]λ (nm): +60 (589), +69 (578),
+133 (546) (c 0.124, CHCl3).
X-ray Structure Determination. X-ray data for compound
(R,Sp)-8 were collected on a Bruker Smart APEX CCD area detector
diffractometer using graphite-monochromated Mo KR radiation
(λ ) 0.71073 Å) and 0.3° ω-scan frames covering a complete sphere
Supporting Information Available: Full experimental details
for all compounds; CIF file of compound (R,Sp)-8. This material is
available free of charge via the Internet at http://pubs.acs.org.
(41) Bruker programs: SMART, version 5.629; SAINT+, version 6.45;
SADABS, version 2.10; SHELXTL, version 6.14; Bruker AXS Inc.: Madison,
WI, 2003.
(42) Sheldrick, G. M. SHELX97, Program System for Crystal Structure
Determination; University of Go¨ttingen: Go¨ttingen, Germany, 1997.
OM7003282